Alcohol addiction continues to be a substantial medical, social, and financial problem in the United States. The dynamic process of alcohol addiction involves a transition from recreational alcohol use and deteriorates over time into excessive or compulsive drinking. Given that alcoholism is a chronic relapsing disease, it is not uncommon for many alcoholics to experience periods of drinking followed by periods of abstinence. This cyclic pattern of alcohol intake and deprivation may have severe consequnces on drinking behavior, including excessive or 'binge-like' consumption. There is very little pre-clinical information on the environmental and biological factors that mediate relapse-like alcohol drinking. Most basic reasearch using animal models has concentrated on the initiation and maintenance phases of alcohol intake. However, alcohol cosumption data (limited or continous access) by such approaches shows little variation over time (i.e., stable patterns of alcohol intake), thus fails to capture a fundamental characteristic of the addiction process. Thus, a goal has been to develop behavioral models that reflect the transition from controlled alcohol use to excessive consumption. A primary experimental approach to study relapse-like drinking has [unreadable] been through the expression of the alcohol deprivation effect (ADE), which is measured by an increase in alcohol intake and preference over baseline drinking conditions after a period of abstinence. The focus and overall objective of this proposal is to is employ a C57BL/6 model of repeated alcohol deprivations and relapse-like drinking to identify the neurobiological events that contribute to relapse. Conceivably, changes in extracellular glutamate levels the prefrontal cortex and ventral striatum may represent key neural substrates and neurochemical events critical in mediating relapse drinking behavior. To date, there is very little information available about changes in glutamatergic transmission that may relate to alcohol relapse. Therefore, a unique and novel feature of this proposal is to combine a robust C57BL/6 model of alcohol relapse drinking with in vivo microdialysis and site specific microinjections to validate the relevance of glutamatergic alterations in the prefrontal-ventral striatal pathway. Research to this end could potentially lead to pharmacotherapies that might reduce relapse risk and craving states. [unreadable] [unreadable] [unreadable]